Comorbidities of systemic lupus erythematosus prior to and following diagnosis in different age-at-onset groups.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a female-dominated autoimmune disease that can occur at any age and has a diverse course. The clinical manifestation of this disease can vary depending on the patient's age at onset. The aim of this study was to characterise the comorbidities at the time of SLE diagnosis and after in different age groups. METHODS: A total 1042 incident cases of SLE with a Catastrophic Illness Card in 2005 and 10,420 age- and sex-matched controls from the general population registered in the National Health Insurance Research Database in Taiwan were enrolled in the study. The risk of comorbidities before (adjusted odds ratio, [aOR]) and after (adjusted hazard ratio, [aHR]) of SLE was analysed. The burden of these SLE-associated comorbidities was weight by the Charlson comorbidity index (CCI). We used the cumulative incidence to evaluate the impact of comorbidities on different age onset groups. RESULTS: In this study, musculoskeletal diseases had the highest positive association (aOR, 5.29; 95% confidence interval [CI]: 4.25-6.57) prior to the diagnosis of SLE and they were also the most common developing incident comorbidity after the diagnosis (HR, 13.7; 95% CI: 11.91-15.77). It only took less than 1 year for 50% of the late-onset SLE patients to develop any increase in CCI score. The developing comorbidities attributed to 16.3% all-cause mortality and they had the greatest impact on late-onset SLE patients, with 33.3% cumulative incidence to all-cause mortality. There is no difference in the incidence of infectious diseases across different age groups. The herpes zoster infection had the greatest cumulative incidence among the category of infection diseases in child-onset SLE patients. CONCLUSION: SLE patients had increased risks of multiple pre-existing comorbidities at diagnosis. The developed comorbidity after diagnosis could contribute to all-cause mortality. The herpes zoster infection is primarily an issue in child-onset SLE patients.

Incidence and prevalence of Tourette syndrome and chronic tic disorders in Taiwan: a nationwide population-based study.

PURPOSE: The incidence of Tourette syndrome and chronic tic disorders has seldom been evaluated in Asia. METHODS: Using the National Taiwan Insurance Research Database, the annual standardized incidence and prevalence of Tourette syndrome (TS) and chronic tic disorders were estimated from 2007 to 2015. The pre-existing comorbidity at disease diagnosis was also evaluated. RESULTS: From 2007 to 2015, the age- and sex-standardized incidence increased from 5.34 (95% confidence interval [CI] 5.06-5.62) per 100,000 person-years to 6.87 (95% CI 6.53-7.21) per 100,000 person-years. In children and adolescents, the age- and sex-standardized incidence increased from 19.58 (95% CI 18.42-20.75) per 100,000 person-years to 31.79 (95% CI 30.09-33.49) per 100,000 person-years. In adults, the age- and sex-standardized incidence decreased from 2.01 (95% CI 1.79-2.23) per 100,000 person-years to 1.24 (95% CI 1.07-1.42) per 100,000 person-years. The incidence rate ratio (IRR) between males and females was 3.74 (95% CI 3.32-4.22). The age- and sex-standardized prevalence increased from 37.51 (95% CI 36.75-38.27) per 100,000 people in 2007 to 84.18 (95% CI 83.02-85.35) per 100,000 people in 2015. The rate risk (RR) between males and females was 3.65 (95% CI 3.53-3.78). CONCLUSION: The annual incidence rates of TS and chronic tic disorders increased in childhood and adolescence but decreased in adulthood from 2007 to 2015. The prevalence rates increased over the same period.

Secular Trends in the Incidence, Prevalence, and Medications for Epilepsy from 2007 to 2015 in Taiwan: A Nationwide Population-Based Study.

BACKGROUND: Patients with epilepsy have a higher mortality rate than the general population. Up-to-date estimates of epilepsy incidence, prevalence, and medication use are critical to assist policymaking. METHODS: Using the National Taiwan Insurance Research Database, the standardized incidence and prevalence of epilepsy were estimated in each calendar year from 2007 to 2015. We used the incident cases of epilepsy to analyze the change in prescribing patterns from 2007 to 2015. Joinpoint regression was used to estimate secular trends. RESULTS: From 2007 to 2015, the age- and sex-standardized incidence decreased from 0.72 (95% confidence interval [CI] 0.70-0.73) to 0.54 (95% CI 0.53-0.55) per 1,000 person-years, giving an annual percentage change (APC) of -2.73 (p < 0.05). Among patients younger than 20 years, the incidence did not change significantly. The age- and sex-standardized prevalence decreased from 6.94 (95% CI 6.90-6.98) to 6.86 (95% CI, 6.82-6.89) per 1,000 people, giving an APC of -0.31 (p < 0.05). However, the prevalence increased in the 35- to 49- and 50- to 64-year age-groups. The most common first-line anticonvulsant was phenytoin in 2007 and valproate in 2015. The use of levetiracetam, clobazam, and valproate increased during the study period, with APCs of 25.48% (95% CI 19.97-31.24), 6.41 (3.09-9.85), and 2.83 (1.51-4.16), respectively. The use of carbamazepine, phenytoin, and topiramate decreased; the APCs were -23.86% (95% CI -25.25 to -22.44), -6.61 (-8.40 to -4.79), and -4.29% (-7.87 to -0.57), respectively. CONCLUSIONS: The overall prevalence and incidence of epilepsy decreased slightly from 2007 to 2015. The prescribed first-line anticonvulsant also changed over time.

Prevalence and risk of thyroid diseases in myasthenia gravis.

OBJECTIVES: To estimate the prevalence of thyroid diseases and the cumulative risk of thyroid diseases during a follow-up period after myasthenia gravis (MG) diagnosis compared with non-MG controls. MATERIALS AND METHODS: We used the Taiwan National Health Insurance Database linked to Registry of Catastrophic Illness database to identify patients with MG. The controls were composed of those who did not have MG and were matched with the MG patients by sex, age, and the index date. We recorded thyroid disease histories before and after the index date. RESULTS: Our study included 5813 MG patients and 29 065 controls. The prevalence of thyroid diseases in the MG patients at diagnosis was 18.4%, which was nearly 3.9-fold greater than that in the control group. (Odds ratio [OR] 3.895, 95% Confidence interval [CI] 3.574-4.246) After excluding pre-existing thyroid diseases, the incidence of comorbid thyroid diseases was 8.7% in the MG patients and 4% in the control group. The MG patients had a 2.36-fold increased risk of developing thyroid diseases compared to the control group. (crude hazard ratio [HR] 2.360, 95% CI 2.095-2.659) The cumulative probabilities of developing thyroid diseases at 1, 5, and 10 years after the index date were 21.6%, 24.9%, and 28.7%, respectively, in the MG patients, while the cumulative probabilities were 6.5%, 8.8%, and 11.8%, respectively, in control group (log-rank test <0.0001). CONCLUSIONS: The current population-based study showed a higher prevalence of pre-existing thyroid diseases and a higher cumulative probability of thyroid diseases during follow-up after MG diagnosis than in the general population.

Temporal relationships between systemic lupus erythematosus and comorbidities.

OBJECTIVE: To examine the burden of comorbidities prior to and after the diagnosis of SLE and its impact on mortality. METHODS: We identified 1605 incident cases of SLE and 6284 matched controls from the UK primary care. The risks of comorbidities before (prevalence; odds ratios) and after SLE diagnosis (incidence; hazard ratios) and the impact of comorbidities at diagnosis on all-cause mortality were estimated. RESULTS: At diagnosis, SLE was associated with adjusted odds ratios (95% CI) of 2.25 (1.97-2.56), 3.37 (2.49-4.57) and 3.54 (1.89-6.63) for a Charlson comorbidity index of 1-2, 3-4 and ≥5, respectively. Following diagnosis, SLE also associated with increased risk of developing any comorbidity with an adjusted hazard ratio (95% CI) of 1.30 (95% CI, 1.13-1.49). At diagnosis, SLE was associated with a greater risk of cancer, cardiovascular, renal, liver, rheumatological and neurological diseases as well as depression, anaemia and psoriasis. Risks of developing incident comorbidity in the categories of neoplasm, cardiovascular, genitourinary, metabolic/endocrine, gastrointestinal and hepatic diseases, chronic pulmonary diseases, musculoskeletal/connective tissue and neurological diseases were higher in SLE patients. People with SLE had higher mortality risk compared with controls, with adjusted hazard ratio of 1.91 (95% CI, 1.62-2.26); after further adjusting for comorbidities this reduced to 1.64 (1.37-1.97). Comorbidities at SLE diagnosis accounted for 27.6% of the apparent difference in mortality between SLE patients and matched controls. CONCLUSION: People with SLE have increased risks of multiple comorbidities both prior to and after diagnosis and this contributes significantly to all-cause mortality.

Correlation of anti-acetylcholine receptor antibody levels and long-term outcomes of juvenile myasthenia gravis in Taiwan: a case control study.

BACKGROUND: Myasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis. METHODS: Patients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic. RESULTS: A total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161). CONCLUSIONS: Juvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.

Association of maternal ethnicity and urbanicity on severe pediatric disease: a nationwide cohort study.

BACKGROUND: A healthy migrant effect on birth outcomes has been reported, however, whether this protective effect persists throughout childhood is unknown. The effect of urbanicity on child health among an immigrant population is unclear. The objective of this study was to compare the incidence rate and cumulative incidence of severe diseases among urban children of Taiwan-born mothers, rural children of Taiwan-born mothers, urban children of foreign-born mothers, and rural children of foreign-born mothers. METHODS: A nationwide cohort study was conducted for children born in Taiwan during 2004-2011 and follow-up till age 4 to 11 years old by linkage the Taiwan Birth Registry 2004-2011, Taiwan Death Registry 2004-2015, and National Health Insurance Research Database 2004-2015. Cox proportional hazards model (multivariable) was used to examine differences among the four study groups. RESULTS: There were 682,982 urban children of Taiwan-born mothers, 662,818 rural children of Taiwan-born mothers, 61,570 urban children of foreign-born mothers, 87,473 rural children of foreign-born mothers. Children of foreign-born mothers had a lower incidence of vasculitis, mainly Kawasaki disease. The incidences of congenital disorders did not differ between children of foreign-born mothers and children of Taiwan-born mothers. The incidence of psychotic disorders was higher in urban children. However, children in rural areas had a higher incidence of major trauma/burn and a higher mortality rate. CONCLUSIONS: A healthy migrant effect was only seen for Kawasaki disease. The mental health of urban children born to immigrant mothers warrants concern.

Urate-lowering treatment and risk of total joint replacement in patients with gout.

Objectives: To examine whether gout is an independent risk factor for total joint replacement (TJR) and whether urate-lowering treatment (ULT) reduces this risk. Methods: Using the Taiwan National Health Insurance database and the UK Clinical Practice Research Datalink, 74 560 Taiwan patients and 34 505 UK patients with incident gout were identified and age and sex matched to people without gout. Cox proportional hazards models and condition logistic regression were used to examine the risk of TJR in gout patients and the association between cumulative defined daily dose (cDDD) of ULT and TJR. Results: The prevalence rates of TJR in the patients at the time of diagnosis of gout and in people without gout were 1.16% vs 0.82% in Taiwan and 2.61% vs 1.76% in the UK. After a gout diagnosis, the incidence of TJR was higher in the patients with gout compared with those without (3.23 vs 1.91 cases/1000 person-years in Taiwan and 6.87 vs 4.61 cases/1000 person-years in the UK), with adjusted HRs of 1.56 (95% CI 1.45, 1.68) in Taiwan and 1.14 (1.05, 1.22) in the UK. Compared with patients with gout with <28 cDDD ULT, the adjusted ORs for TJR were 0.89 (95% CI 0.77, 1.03) for 28-90 cDDD, 1.03 (0.85, 1.24) for 90-180 cDDD and 1.12 (0.94, 1.34) for >180 cDDD ULT in Taiwan. In the UK, the respective ORs were 1.09 (0.83, 1.42), 0.93 (0.68, 1.27) and 1.08 (0.94, 1.24). Conclusion: This population-based study provides evidence from two nation populations that gout confers significant TJR risk, which was not reduced by current ULT.

Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: The first real-world evaluation in Asian pediatric neurology clinics.

AIM: This study investigated the efficacy and safety of perampanel (PER) adjunctive therapy in pediatric patients with epilepsy whose seizures are pharmacoresistant to existing antiepileptic drugs. METHODS: A clinical retrospective study was conducted from 2016 to 2017 in the pediatric neurology clinic at a tertiary children's hospital. We reviewed the data obtained from 66 children whose seizures were pharmacoresistant to more than two antiepileptic drugs, and could be followed up for a minimum of 3 months after PER adjunctive therapy initiation. The efficacy was estimated by the PER response rate at 3-, 6-, and 12-month follow-up evaluations, and adverse events were also recorded. RESULTS: The rate of seizure reduction of >50% was 30.3%, 37.5%, and 34.7% for all seizure types at 3, 6, and 12 months, in which 7.6%, 8.9%, and 14.3% of the patients became seizure-free at these time points, respectively. No significant differences were found between enzyme-inducing and nonenzyme-inducing antiepileptic drugs in combination with PER with regard to the responder rate. Five patients with Dravet syndrome were included in the study. Four of them (80%) exhibited 50% seizure reduction at the last visit, at which point, two patients (40.0%) were seizure-free. The retention rate was 51% at 12 months. Adverse events were documented in 25 patients (35.7%) and led to PER discontinuation in eight patients (12.1%). The most common adverse events comprised irritability, skin rash, dizziness, and somnolence; however, all were transient and successfully managed after PER dose reduction or discontinuation. CONCLUSION: The current data support the value of adjunctive PER in child and adolescent patients with pharmacoresistant epilepsy in daily clinical practice. Perampanel was efficacious and generally well-tolerated as an add-on treatment for epilepsy.

Arterial spin-labeling perfusion imaging of childhood encephalitis: correlation with seizure and clinical outcome.

PURPOSE: In childhood encephalitis, perfusion abnormalities have been infrequently reported to associate with clinical status. We investigated whether perfusion abnormalities correlated with seizure and clinical outcome in encephalitis. METHODS: We retrospectively analyzed the MR studies of 77 pediatric patients with encephalitis. Pseudo-continuous arterial spin-labeling (ASL) imaging was performed on a 3-T scanner. The patients were divided into five groups according to ASL perfusion imaging pattern: normal perfusion (NP), focal hypoperfusion (Lf), extreme global hypoperfusion (LE), focal hyperperfusion (Hf), and extreme global hyperperfusion (HE). Clinical outcome at 3 weeks was dichotomized to unfavorable or favorable outcome according to the Glasgow outcome scale. Multivariate logistic regression was conducted to predict unfavorable outcome and presence of seizure separately, based on explanatory variables including age, sex, and ASL pattern. RESULTS: Twenty-seven (35%) patients were designated as in group Hf, five (7%) in group Lf, 11 (14%) in group LE, none in group HE, and 34 (44%) in group NP. Multivariate logistic regression analysis showed that ASL pattern was significantly associated with unfavorable outcome (P = 0.005) and with presence of seizure (P = 0.005). For ASL pattern, group LE was 17.31 times as likely to have an unfavorable outcome as group NP (odds ratio confidence interval [CI] 3.084, 97.105; P = 0.001). Group Hf was 6.383 times as likely to have seizure as group NP (CI 1.765, 23.083; P = 0.005). CONCLUSIONS: In childhood encephalitis, patients with extreme global hypoperfusion had poor neurological outcome and those with focal hypoperfusion were more likely to have seizure.

Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan.

PURPOSE: We aimed to evaluate the validity of cancer diagnosis in the National Health Insurance (NHI) database, which has routinely collected the health information of almost the entire Taiwanese population since 1995, compared with the Taiwan National Cancer Registry (NCR). METHODS: There were 26,542,445 active participants registered in the NHI database between 2001 and 2012. National Cancer Registry and NHI database records were compared for cancer diagnosis; date of cancer diagnosis; and 1, 2, and 5 year survival. In addition, the 10 leading causes of cancer deaths in Taiwan were analyzed. RESULTS: There were 908,986 cancer diagnoses in NCR and NHI database and 782,775 (86.1%) in both, with 53,192 (5.9%) in the NHI database only and 73,019 (8.0%) in the NCR only. The positive predictive value of the NHI database cancer diagnoses was 94% for all cancers; the positive predictive value of the 10 specific cancers ranged from 95% (lung cancer) to 82% (cervical cancer). The date of diagnosis in the NHI database was generally delayed by a median of 15 days (interquartile range 8-18) compared with the NCR. The 1, 2, and 5 year survival rates were 71.21%, 60.85%, and 47.44% using the NHI database and were 71.18%, 60.17%, and 46.09% using NCR data. CONCLUSIONS: Recording of cancer diagnoses and survival estimates based on these diagnosis codes in the NHI database are generally consistent with the NCR. Studies using NHI database data must pay careful attention to eligibility and record linkage; use of both sources is recommended.

Familial Aggregation and Heritability of Congenital Heart Defects.

BACKGROUND: Congenital heart defects (CHD) are known to cluster within families, but existing evidence varies for the estimates of familial relative risk (RR). We aimed to examine familial aggregation and heritability of CHD in the general population of Taiwan.Methods and Results:We conducted a population-based family study using the Taiwan National Health Insurance (NHI) research database. Individuals with affected first-degree (n=295,636) or second-degree (n=73,985) relatives were identified from all NHI beneficiaries (n=23,422,955) registered in 2012. Diagnoses of CHD for all study subjects were ascertained between January 1, 1996 and December 31, 2012. Having a twin, a first-degree relative and an affected second-degree relative were associated with an adjusted RR of 12.03 (11.59-12.49), 4.91 (4.85-4.97) and 1.21 (1.14-1.28) for CHD, respectively. Individuals with 1 affected first-degree relative had a RR of 4.78 (4.72-4.84), and those with ≥2 had an RR of 7.10 (6.77-7.45) for CHD. The estimated accountability for phenotypic variance of CHD was 37.3% for familial transmission and 62.8% for non-shared environmental factors. CONCLUSIONS: Our results indicated that CHD tend to cluster within families, and approximately one-third of phenotypic variance was explained by familial factors.

Association Between Use of Non-Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation.

Importance: Non-vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective: To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants: Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016. Exposures: NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin. Main Outcomes and Measures: Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. Results: Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P < .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone. Conclusions and Relevance: Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs.

Paediatric Multiple Sclerosis: Update on Diagnostic Criteria, Imaging, Histopathology and Treatment Choices.

Paediatric multiple sclerosis (MS) represents less than 5 % of the MS population, but patients with paediatric-onset disease reach permanent disability at a younger age than adult-onset patients. Accurate diagnosis at presentation and optimal long-term treatment are vital to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it may be difficult to early differentiate paediatric MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD), as they often have atypical presentation that differs from that of adult-onset MS. The purpose of this review is to summarize the updated views on diagnostic criteria, imaging, histopathology and treatment choices.

Histogram analysis of quantitative T1 and MT maps from ultrahigh field MRI in clinically isolated syndrome and relapsing-remitting multiple sclerosis.

This study used quantitative MRI to study normal appearing white matter (NAWM) in patients with clinically isolated syndromes suggestive of multiple sclerosis and relapsing-remitting multiple sclerosis (RRMS). This was done at ultrahigh field (7 T) for greater spatial resolution and sensitivity. 17 CIS patients, 11 RRMS patients, and 20 age-matched healthy controls were recruited. They were scanned using a 3D inversion recovery turbo field echo sequence to measure the longitudinal relaxation time (T1). A 3D magnetization transfer prepared turbo field echo (MT-TFE) sequence was also acquired, first without a presaturation pulse and then with the MT presaturation pulse applied at -1.05 kHz and +1.05 kHz off resonance from water to produce two magnetization transfer ratio maps (MTR(-) and MTR(+)). Histogram analysis was performed on the signal from the voxels in the NAWM mask. The upper quartile cut-off of the T1 histogram was significantly higher in RRMS patients than in controls (p < 0.05), but there was no difference in CIS. In contrast, MTR was significantly different between CIS or RRMS patients and controls (p < 0.05) for most histogram measures considered. The difference between MTR(+) and MTR(-) signals showed that NOE contributions dominated the changes found. There was a weak negative correlation (r = -0.46, p < 0.05) between the mode of T1 distributions and healthy controls' age; this was not significant for MTR(+) (r = -0.34, p > 0.05) or MTR(-) (r = 0.13, p > 0.05). There was no significant correlation between the median of T1, MTR(-), or MTR(+) and the age of healthy controls. Furthermore, no significant correlation was observed between EDSS or disease duration and T1, MTR(-), or MTR(+) for either CIS or RRMS patients. In conclusion, MTR was found to be more sensitive to early changes in MS disease than T1.

Clinical features and outcomes of invasive pneumococcal disease in a pediatric intensive care unit.

BACKGROUND: Invasive pneumococcal disease (IPD) results in high morbidity and mortality globally each year, although it is a vaccine-preventable disease. This study aimed to characterize the clinical features of IPD in a pediatric intensive care unit (PICU) in Taiwan. The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in the private sector in October 2005. The estimated coverage rate of PCV7 vaccination in 2010 was 45.5% among children <5 years of age. METHODS: We conducted a retrospective study at a single center in northern Taiwan for invasive pneumococcal disease in a PICU from 2009 to 2013. Demographic characteristics, clinical courses, serotype, antibiotic susceptibility, and outcomes were analyzed. RESULTS: Over the 5-year study period, 2167 patients were admitted to the PICU; 48 (2.2%) had IPD. There were 29 female and 19 male patients. Their mean age was 3.7 years (range 0.7-12.5 years, with the peak age at 2-5 years; n = 30, 63%). Pneumonia was the most frequent type (n = 38, 79%), followed by meningitis (n = 10, 21%). In total, three patients died, all within 72 h after admission; the final diagnoses were all meningitis. Thirty-four children with pneumonia received chest tube insertion for pleural effusion drainage. Of them, 22 (65%) finally still underwent video-assisted thoracoscopic surgery. Eight (17%) children had hemolytic uremic syndrome, and seven of them underwent hemodialysis. In total, 37 serotypes were detected; 95% were covered by PCV13. Serotype 19A was most common (54%) overall; however, in those with meningitis, serotype 19 F was most common. CONCLUSIONS: Meningitis is the most severe type of invasive pneumococcal disease in our pediatric intensive care unit. It may progress rapidly even when subjects are given antibiotics promptly. The most common serotype in meningitis is 19 F, which is vaccine preventable. Thus, universal mass pneumococcal vaccination is still needed.

Significance of serum uric acid levels on the risk of all-cause and cardiovascular mortality.

OBJECTIVE: To assess the associations between serum uric acid (SUA) level and mortality. METHODS: The study included 354 110 subjects without a history of gout and whose SUA levels were tested at Chang Gung Memorial Hospital in Taiwan. Cox regression models were used to estimate hazard ratios and 95% CIs for mortality in six predefined SUA strata (≤0.17, 0.18-0.29, 0.30-0.41, 0.42-0.53, 0.54-0.65 and ≥0.66 mmol/l), after adjusting for age, sex, SUA stratum, estimated glomerular filtration rate, fasting glucose, total cholesterol and history of hypertension, diabetes mellitus, coronary heart disease, stroke, heart failure or chronic kidney disease. RESULTS: There were 33 562 all-cause deaths during the study period. Crude all-cause mortality rates across the SUA strata were 52.5, 19.7, 17.4, 20.0, 28.0 and 41.1 deaths per 1000 person-years. Using the stratum 3 of SUA as a reference, the age- and sex-adjusted hazard ratios (95% CIs) across SUA strata were 2.79 (2.62, 2.96), 1.32 (1.28, 1.36), 1.00, 1.10 (1.07, 1.14), 1.42 (1.37, 1.48) and 2.12 (2.01, 2.23) for all-cause mortality; 2.24 (1.93, 2.59), 1.18 (1.10, 1.27), 1.00, 1.21 (1.14, 1.29), 1.74 (1.60, 1.88) and 2.53 (2.28, 2.81) for cardiovascular mortality and 3.41 (3.11, 3.73), 1.48 (1.42, 1.55), 1.00, 0.88 (0.84, 0.92), 0.91 (0.85, 0.98) and 1.23 (1.11, 1.36) for cancer-related mortality. CONCLUSION: Individuals with SUA levels at either extremes are at higher risk for all-cause and cardiovascular mortality. SUA levels of 0.30-0.41 mmol/l were associated with the lowest mortality rate and should be regarded as optimal.

Risk of myocardial infarction among patients with gout: a nationwide population-based study.

OBJECTIVE: To investigate the association between gout and myocardial infarction (MI) in a representative cohort in Taiwan. METHODS: Data were collected from the Taiwan National Health Insurance database. Adults >20 years of age without history of MI were included. Patients were considered to have gout if they received a diagnosis of gout requiring medical treatment. Multivariate Cox proportional hazards models were used to evaluate the risk of MI in gout patients. RESULTS: Of the 704 503 patients included, 26 556 (3.8%) had gout. In total, 3718 (with gout, n = 463; without gout, n = 3255) patients had an MI, 299 (with gout, n = 35; without gout, n = 264) of whom died. The incidence of MI was 2.20 and 0.60 per 1000 patient-years in individuals with and without gout, respectively (log-rank test, P < 0.001). After adjustment for age, sex and history of diabetes mellitus, hypertension, coronary heart disease (CHD), stroke and end-stage renal disease, gout was associated with MIs [hazard ratio (HR), 1.23] and non-fatal MIs (HR, 1.26). In individuals without cardiovascular risk factors, gout was associated with MIs (HR 1.84; 95% CI 1.51, 2.24) and non-fatal MIs (HR 1.80; 95% CI 1.49, 3.95), after adjustment for age and sex. Moreover, in our study population, the HRs for MI decreased as age increased. CONCLUSION: Gout is an independent risk factor for MI, and the increased risk of MI is present even in young people and those without cardiovascular risk factors.

Rheumatoid arthritis prevalence, incidence, and mortality rates: a nationwide population study in Taiwan.

There are few nationwide population studies on the epidemiology of rheumatoid arthritis (RA). Here, we present the epidemiologic features and mortality rates of RA in Taiwan. The catastrophic illness registry of the Taiwan National Health Insurance Research Database and the National Death Registry of Taiwan were used to estimate the incidence and prevalence of RA and its associated mortality rates. All-cause and cause-specific standardized mortality ratios (SMRs) were calculated and compared to the corresponding ratios of the general population in 2002. The study comprised 15,967 incident RA cases (3,562 men; 12,405 women) occurring from 2002 through 2007. The annual incidence of RA was 15.8 cases (men, 10.1; women, 41.0) per 100,000 population. The period prevalence was 97.5 cases (men, 37.4; women, 159.5) per 100,000 population. During 67,010 person-years of follow-up, 985 deaths (372 men; 613 women) were identified, and this corresponded to a crude mortality rate of 14.7 deaths (men, 25.0; women, 11.8) per 1,000 person-years. Compared to female patients, male patients had a higher risk for mortality (log-rank test, p < 0.001). RA patients had an SMR of 1.25 (95 % confidence interval [CI], 1.18-1.33) for all-cause mortality. Compared to the general population, RA patients of both genders in this cohort had a significantly higher risk of mortality from infection (SMR, 2.49) and gastrointestinal diseases (SMR, 1.76). RA incidence and prevalence were higher in women than in men. Mortality was higher in men than in women. Compared to the general population, RA patients had a higher risk of death, particularly from infection and gastrointestinal diseases.